title: A mouse model that recapitulates cardinal features of the 15q13.3 microdeletion syndrome including schizophrenia- and epilepsy-related alterations.
abstract: BACKGROUND
  Genome-wide scans have uncovered rare copy number variants conferring high risk of psychiatric disorders. The 15q13.3 microdeletion is associated with a considerably increased risk of idiopathic generalized epilepsy, intellectual disability, and schizophrenia.
  
  
  METHODS
  A 15q13.3 microdeletion mouse model (Df[h15q13]/+) was generated by hemizygous deletion of the orthologous region and characterized with focus on schizophrenia- and epilepsy-relevant parameters.
  
  
  RESULTS
  Df(h15q13)/+ mice showed marked changes in neuronal excitability in acute seizure assays, with increased propensity to develop myoclonic and absence-like seizures but decreased propensity for clonic and tonic seizures. Furthermore, they had impaired long-term spatial reference memory and a decreased theta frequency in hippocampus and prefrontal cortex. Electroencephalogram characterization revealed auditory processing deficits similar to those observed in schizophrenia. Gamma band power was increased during active state, but evoked gamma power following auditory stimulus (40 Hz) was dramatically reduced, mirroring observations in patients with schizophrenia. In addition, Df(h15q13)/+ mice showed schizophrenia-like decreases in amplitudes of auditory evoked potentials. Although displaying a grossly normal behavior, Df(h15q13)/+ mice are more aggressive following exposure to mild stressors, similar to what is described in human deletion carriers. Furthermore, Df(h15q13)/+ mice have increased body weight, and a similar increase in body weight was subsequently found in a sample of human subjects with 15q13.3 deletion.
  
  
  CONCLUSIONS
  The Df(h15q13)/+ mouse shows similarities to several alterations related to the 15q13.3 microdeletion syndrome, epilepsy, and schizophrenia, offering a novel tool for addressing the underlying biology of these diseases.
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Fejgin
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Birknow
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Jesper F
authors.initials: JF
authors.lastname: Bastlund
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Nielsen
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Jes B
authors.initials: JB
authors.lastname: Lauridsen
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Stacy
authors.initials: S
authors.lastname: Steinberg
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby.
authors.forename: Helge B D
authors.initials: HB
authors.lastname: Sorensen
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby.
authors.forename: Troels E
authors.initials: TE
authors.lastname: Mortensen
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Larsen
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Ib V
authors.initials: IV
authors.lastname: Klewe
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Søren V
authors.initials: SV
authors.lastname: Rasmussen
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Werge
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Pekka
authors.initials: P
authors.lastname: Kallunki
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Christensen
authors.affiliation: Neuroscience Research DK, H. Lundbeck A/S, Valby, Denmark. Electronic address: MDI@lundbeck.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Didriksen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000503:physiopathology*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics*; D012640:Seizures / Q000235:genetics*
keywords: Absence seizures; Chrna7; PTZ; animal model; copy number variation; gamma oscillations